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Assessment of Cardiac Function
The accurate and reproducible assessment of cardiac function is a fundamental aim of noninvasive cardiac imaging. It forms the foundation upon which much of the assessment and management of myocardial dysfunction, ischemia, viability, remodeling, valvular, and other cardiac disorders are based. In this chapter, we discuss the importance of the measurement of global cardiac function, compare techniques, show differences according to magnetic fields, provide a practical step-by-step guide to its assessment by cardiovascular magnetic resonance (CMR) and describe new techniques that can be used for the assessment of cardiac function.
The Population Impact of Cardiac Dysfunction
Cardiac dysfunction can result from a broad spectrum of organ-specific and multisystem disorders. The defining property that all these disorders have in common is impairment of the ventricle's ability to eject blood, which, in its broadest sense and omitting any discussion of semantics, is known as heart failure. Heart failure is common, with approximately 1.5% to 2% of the population below 65 years old being affected, rising to 6% to 10% of those older than 65 years. It afflicts 4.8 million people in the United States, with 400,000 to 700,000 new cases developing each year. It is the leading cause of hospital admission in people older than 65 years of age, and despite the fact that survival has improved over time, the death rate remains high: ≈50% of people diagnosed with heart failure will die within 5 years. The number of any-mention deaths attributable to heart failure was approximately as high in 1995 as it was in 2011, although projections show that the prevalence of heart failure will increase 46% from 2012 to 2030, resulting in over 8 million people 18 years old and older with heart failure in the United States. Consequently, heart failure is an enormous consumer of health care budgets in the Western world, and treatments to prevent occurrence, to slow its progression, or to prevent repeated hospitalizations can have an important economic impact.
The Importance of Measuring Cardiac Function
A single assessment of cardiac function can provide important diagnostic and prognostic information, whether in the setting of postinfarction recovery, left ventricular (LV) hypertrophy, or chronic heart failure. As well as improving symptoms and quality of life, treatment of heart failure aims to decrease the likelihood of disease progression that could result in costly hospital admissions and ultimately death. To allow early evaluation and alteration of an individual patient's management, serial studies need to be performed using a technique that not only is accurate but also has good interstudy reproducibility. This principle also applies in considering study populations of trial therapies.
Techniques for Assessing Cardiac Function
Bedside clinical assessment of cardiac function is generally poor, and electrocardiogram (ECG) findings are nonspecific, although the presence of an entirely normal ECG has a 95% likelihood of normal systolic function. In the search for a better assessment, it is worth considering the ideal imaging technique. This would provide a noninvasive, accurate, and reproducible assessment of cardiac function without exposure to ionizing radiation. It would be widely available and would be time- and cost-effective. Although no technique meets these ideals, there are clear differences between modalities that merit discussion.
Echocardiography
Echocardiography is a widely available but less than ideal imaging technique for quantifying cardiac function because the image acquisition is operator and acoustic window dependent. The quantification of ventricular function is limited by a priori geometric assumptions that may provide a reasonable assessment in the normal ventricle but are less reliable in remodeled hearts, owing to complex irregular shape changes. M-mode echocardiography was developed in the early 1970s and was immediately applied in practice for LV function assessment, because of its simple algorithm and noninvasiveness. In this technique, mid-LV diameters are measured in the minor axis ( Fig. 16.1 ), and volumes are obtained by cubing these values (thereby cubing the errors). Functional estimates, such as fractional shortening and ejection fraction (EF), are then derived from these diameters and volumes, respectively. This method assumes a number of facts that are not always true: that the minor-axis view is strictly perpendicular to the LV long axis, that a single view is representative of all the myocardial segments, and that contraction is uniform throughout the ventricle. Two-dimensional echocardiography (2DE), with the ability of imaging the heart in tomographic views, considerably improved the accuracy of LV volume measurement, providing the opportunity to derive the cardiac function from cardiac volumes by the area-length and modified Simpson's method of discs ( Fig. 16.2 ). This, however, relies on assuming that the left ventricle has a uniform shape with no regional wall motion abnormalities and on good visualization of the entire endocardial border, which is frequently not possible, although several software-based algorithms for automatic endocardial border detection and online calculation of LV volume have been developed. For example, in a multicenter study that required good-quality echocardiograms as an entry criterion, the echo core laboratory was unable to perform a confident two-dimensional (2D) analysis in 31% of patients. Thus being the most frequently used modality in clinical practice, echocardiography has gained limited acceptance in clinical trials, owing to its moderate reproducibility and accuracy to define LV ejection fraction (LVEF), because of geometric assumptions, poor acoustic windows, foreshortening of the ventricle, and inadequate discrimination of the endocardial border. Overall, the practical difficulties of quantifying global function by echo are underlined by the fact that, in the “real world,” it is often simply estimated by the clinician performing the imaging. This is highly subjective but can be clinically valid with experience. Other echocardiographic methods, derived from Doppler analysis, have been validated for evaluation of global myocardial performance that do not require geometric assumptions and do not rely on endocardial border delineation. These include for instance the Tei index, which is less load dependent, the d P /d t , which requires mitral regurgitation to be present, and tissue Doppler mitral annular systolic velocity. However, these methods require a good alignment of the ultrasound beam with flow or myocardial motion and have not been really implemented for daily clinical use. Some years ago, two advances in echocardiography helped improve accuracy and reproducibility of ventricular function assessment. On the one hand, contrast echocardiography has been shown to allow improved assessment of LV volumes and LVEF, with low interobserver variability, thanks to better endocardial border delineation, thus improving the assessment of LV dimensions and wall motion ( Fig. 16.3 ). On the other hand, three-dimensional (3D) echocardiography has emerged as a more accurate and reproducible approach to LV quantitation by removing the need for geometric assumptions and eliminating the errors caused by foreshortened apical views. Volumetric analysis of real-time 3D echocardiographic data allows fast dynamic measurement of LV volumes. 3D echocardiography has good reproducibility and good agreement with CMR measurements of LVEF, whereas the agreement of volumes is worse. Although in the past this technique needed a stable cardiac rhythm and constant cardiac function during a moderately long acquisition, recent developments have allowed a full pyramidal dataset to be acquired in a single heartbeat, during a short breath-hold, thus eliminating motion artifacts, and without the need for off-line reconstruction. Still, issues such as its low temporal resolution, lateral attenuation, dependency on acoustic window and on endocardial border delineation, and practicality in clinical practice still remain to be fully assessed as more experience is gained. The use of contrast may overcome some of these limitations. A recent multicenter study has shown that contrast administration on 3D echocardiography results in improved determination of LV volumes and reduced interreader variability. Finally, speckle-tracking imaging is a relatively new tool to assess LV function through measurement of myocardial strain, with a high temporal and spatial resolution, and a better inter observer and intraobserver reproducibility compared with Doppler strain. It is angle independent, not affected by translation cardiac movements, and can assess simultaneously the entire myocardium along all the 3D geometrical (longitudinal, circumferential, and radial) axes. Again, there are pitfalls such as low spatial and temporal resolution of this technique, reproducibility problems across vendors, and lack of wide availability of the technique, which currently is used in the clinical setting, mainly for monitoring cancer therapy–related cardiotoxicity.
Nuclear Cardiology
Nuclear cardiology with radionuclide ventriculography with either Tc-99m-labeled red blood cells or human serum albumin is commonly used to measure ventricular function by measuring the LVEF, with high accuracy and reproducibility, but it has relatively low spatial and temporal resolution, and preparation and scanning times are relatively prolonged. In addition, ventricular volumes are difficult to measure and are rarely performed clinically, and ventricular mass cannot be obtained. Furthermore, the accuracy of the LVEF obtained with a multigated acquisition (MUGA) scan decreases in patients with irregular heart rhythms. Last but not least, with this scan the patient is exposed to an amount of radiation of up to 6 mSv, which is roughly twice the normal background radiation a person receives in 1 year. Consequently, this technique is very rarely used today for ventricular function analysis, not even for monitoring cardiotoxicity of cancer therapies which used to be its main indication. The use of gated perfusion single-photon emission computed tomography (gSPECT) has allowed the development of 3D solutions to global and regional ventricular function, and this has achieved widespread use, especially in the United States. This technique is most useful when perfusion needs to be assessed, and it adds prognostic value to the stress perfusion assessment ; however, it is very rarely performed solely to assess ventricular function ( Fig. 16.4 ). This technique has good reproducibility both for ejection fraction and ventricular volumes, but there are a high number of variables that can affect accuracy, and must be carefully taken care of, including (1) acquisition variables, such as count density per frame, frame rate, or acquisition protocol; (2) processing variables, including reconstruction algorithm, filtering, automation, definition of endocardium and epicardium, definition of hypoperfused walls and valve plane; and (3) patient-dependent variables like heart rate variability, arrhythmia, patient motion, extracardiac uptake close to the LV, small and large left ventricles, and hypoperfused areas. There is special concern in both small and large ventricles because of the limited spatial resolution and the problems of assigning, either manually or automatically, a ventricular border in areas of transmural infarction and thinning where counts are very low. Tc-99m sestamibi ECG-gated SPECT can predict ventricular remodeling in patients with ischemic cardiomyopathy, but 3D echocardiography seems to be more accurate than gated SPECT for estimation of LV remodeling. With respect to radiation dose, advances in hardware, including ultrahigh-sensitivity detectors, dedicated geometry, shorter scan times and optimized reconstruction, and software, with implementation of improved reconstruction algorithms, have obtained total radiation doses of 4.2 to 6.8 mSv. Recently, ECG-gated F-18 fluorodeoxyglucose positron emission tomography ( 8 F-FDG PET) has been shown to be reasonably accurate for measurement of cardiac function, but this technique is expensive, time consuming, and is usually performed only in viability studies. Typical radiation doses for cardiac 18 F-FDG PET scans are now around 7 mSv. Importantly, for all these nuclear cardiology techniques, the need for repeated radionuclide doses in follow-up studies is highly problematic, especially for research, in which radiation exposure must be justified in a milieu of competing technologies and public pressure in general to limit radiation burdens.
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